1. Field of the Invention
The present invention relates generally to the field of molecular biology and virology. More particularly, it concerns Chikungunya polypeptides and viruses that are attenuated in mammalian hosts.
2. Description of Related Art
Chikungunya virus (ChikV is a member of the Togaviridae family; genus Alphavirus (Khan et al., 2002) and is pathogenic to humans. ChikV is an arthropod borne virus (arbovirus) spread by the bite of an aedene mosquito. As with all alphaviruses its genome is composed of a small ˜11 Kb plus polarity single-stranded RNA. The genome encodes 3 structural proteins, E1, E2, and C and 4 nonstructural proteins nsP1-4. As a member of the Togaviruses these viruses are enveloped and as arboviruses they contain a membrane envelope derived from the insect or vertebrate host. The alphavirus genus contains 29 known species which cause encephalitis, fever, and/or arthralgia.
ChikV was first isolated from the blood of a febrile patient in Tanzania in 1953 where the virus was endemic (Pialoux et al., 2007). Outbreaks occur repeatedly in west, central, and southern Africa and have caused several human epidemics in those areas since that time. However, ChikV is a re-emerging pathogenic virus and is now also endemic in south east Asia (see, e.g., the world wide web at searo.who.int/index.htm). Recently, ChikV spread from Asia and the Indian Ocean to Italy (Rezza et al. 2007; Mavalankar et al. 2008). Of the two strain lineages of ChikV, the African; remains enzootic by cycling between mosquitoes and monkeys but the Asian strain is transmitted directly between mosquitoes and humans. This cycle of transmission may have allowed the virus to become more pathogenic as the reservoir host was eliminated (Powers et al., 2000).
In humans, ChikV causes a debilitating disease characterized by fever, headache, nausea, vomiting, fatigue, rash, muscle pain and joint pain; the symptoms commonly associated with Dengue virus infection (with the exception of the arthralgia). Incubation can be 2-12 days, but most commonly 3-7 days with “silent” infections occurring with unknown frequency (WHO, Weekly epidemiological record. 2007). ChikV can be transmitted from mother to child (Ramful et al. 2007) and can produce chronic persisting symptoms including crippling arthralgia, encephalitis and myocarditis (rare) (Paul et al. 2011). ChikV epidemics from 2004-2011 have resulted in 1.4-6.5 million reported cases, with imported cases to 40 countries (Suhrbier et al. 2012). Aedes aegypti is the primary vector of ChikV, but recent outbreaks, which involved mortalities, have been propagated through the Aedes albopictus mosquito (Mavalankar et al. 2008; Dubrulle et al. 2009). Importantly, this mosquito vector has spread to 12 European countries as well as to the Australian continent (Johnson et al. 2008). Despite significant morbidity and mortality associated with ChikV infections and its growing prevalence and geographic distribution there is currently no vaccine or antiviral for ChikV approved for human use (Barrett et al. 2009).